The Role of Gastric Mucosal Immunity in Gastric Diseases.

Gastric mucosa plays its immune function through innate and adaptive immunity by recruiting immune cells and releasing corresponding cytokines, which have an inseparable relationship with gastric diseases. Whether infective gastric diseases caused by Helicobacter pylori, Epstein-Barr virus or other microbe, noninfective gastric diseases, or gastric cancer, gastric mucosal immunity plays an important role in the occurrence and development of the disease. Understanding the unique immune-related tissue structure of the gastric mucosa and its role in immune responses can help prevent gastric diseases or treat them through immunotherapy. In this review, we summarize the basic feature of gastric mucosal immunity and its relationship with gastric diseases to track the latest progress of gastric mucosal immunity, update relevant knowledge and provide theoretical reference for the prevention and treatment of gastric diseases based on the gastric mucosal immunity.

Immunoglobulin G4-Related Disease Manifesting as Isolated, Typical, and Nontypical Gastroesophageal Lesion: A Research of Literature Review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune inflammatory and fibrotic condition. The disease is characterized by tissue infiltration with dense lymphoplasmacytes and IgG4-positive plasma cells. SUMMARY: The aim of this study was to provide gastroenterologists with novel insights into evaluating the gastroesophageal involvement with IgG4-RD or mimickers of this condition and to give special attention to clinicopathological features. A literature review was performed using the PubMed database. A total of 39 studies presenting cases in the form of isolated, typical, and nontypical gastroesophageal involvement with IgG4-RD published between 2010 and 2018 were included. These studies were thoroughly reviewed for symptoms, lesion location, lesion type, lesion size, immune-histopathology, associated diseases, treatment, and follow-up. Of the 39 studies reviewed, 9 were esophageal IgG4-RD lesions, isolated esophageal IgG4-RD 66.66% (6/9), a typical form of esophageal IgG4-RD 11.11% (1/9), and nontypical form esophageal IgG4-RD 22.22% (2/9). The 30 gastric IgG4-RD that include isolated gastric IgG4-RD 46.66% (14/30), typical gastric IgG4-RD 40% (12/30), and nontypical gastric IgG4-RD 13.33% (4/30). The majority of lesions were inflammatory tumors, ulceration, nodular lesions, chronic gastritis, and malignant lesions. Key Messages: IgG4-RD may be manifested by isolated, typical and nontypical forms of gastroesophageal lesions and should be taken into consideration in the differential diagnosis. Corticosteroids may be the sole diagnostic treatment for this condition.

Gastro-allergic anisakiasis: The first case reported in Colombia and a literature review / Anisakiasis gastro-alérgica, primera descripción de un caso en Colombia y revisión bibliográfica

Anisakiasis is a zoonotic parasitic disease caused by consumption of raw or undercooked fish or seafood infected with nematodes of the Anisakis, Pseudoterranova or Contracaecum genera. Here, we describe the first case of anisakiasis in Colombia and summarize the available literature. A 52-year-old female with a history of abrupt-onset sharp epigastric pain, nausea, vomit, diarrhea, and urticaria following fish consumption consulted the health service. The physical examination revealed moderate tenderness of the epigastric region; the laboratory evaluation showed leukocytosis and a simple X-ray and ECG showed no abnormalities. The diagnosis was made by endoscopic examination, which revealed a thickened gastric wall and a moving larval worm. An Anisakis larva was found and extracted endoscopically, which relieved the pain of the patient. Clinically, anisakiasis may present as a gastric, intestinal, extragastrointestinal or allergic disease. Diagnosis and treatment of anisakiasis are made by a dietary history, direct visualization and endoscopic extraction of possible larvae, which is the only effective therapy.

La anisakiasis es una enfermedad parasitaria zoonótica causada por el consumo de pescados o mariscos crudos o poco cocidos infectados con nematodos de los géneros Anisakis, Pseudoterranova y Contracaecum. Se describe el primer caso de anisakiasis en Colombia y se resume la literatura médica disponible. Una mujer de 52 años de edad consultó por dolor epigástrico agudo de inicio abrupto, náuseas, vómitos, diarrea y urticaria después de consumir pescado. El examen físico reveló sensibilidad moderada en el epigastrio. El examen de laboratorio evidenció leucocitosis, en tanto que la radiografía simple y el electrocardiograma no reflejaron ninguna anormalidad. El diagnóstico se hizo mediante una endoscopia de vías digestivas altas, la cual reveló engrosamiento de la pared gástrica y un parásito en movimiento. Se encontró una larva de Anisakis y se la extrajo por endoscopia, lo que alivió el dolor de la paciente. Clínicamente, la anisakiasis puede presentarse como una enfermedad gástrica, intestinal, en otros sistemas o alérgica. El diagnóstico se hace con base en la elaboración del historial alimentario del paciente y la visualización directa de las larvas; el único tratamiento efectivo consiste en su extracción endoscópica.

Anisakiasis gastro-alérgica, primera descripción de un caso en Colombia y revisión bibliográfica / Gastro-allergic anisakiasis: The first case reported in Colombia and a literature review

Resumen La anisakiasis es una enfermedad parasitaria zoonótica causada por el consumo de pescados o mariscos crudos o poco cocidos infectados con nematodos de los géneros Anisakis, Pseudoterranova y Contracaecum. Se describe el primer caso de anisakiasis en Colombia y se resume la literatura médica disponible. Una mujer de 52 años de edad consultó por dolor epigástrico agudo de inicio abrupto, náuseas, vómitos, diarrea y urticaria después de consumir pescado. El examen físico reveló sensibilidad moderada en el epigastrio. El examen de laboratorio evidenció leucocitosis, en tanto que la radiografía simple y el electrocardiograma no reflejaron ninguna anormalidad. El diagnóstico se hizo mediante una endoscopia de vías digestivas altas, la cual reveló engrosamiento de la pared gástrica y un parásito en movimiento. Se encontró una larva de Anisakis y se la extrajo por endoscopia, lo que alivió el dolor de la paciente. Clínicamente, la anisakiasis puede presentarse como una enfermedad gástrica, intestinal, en otros sistemas o alérgica. El diagnóstico se hace con base en la elaboración del historial alimentario del paciente y la visualización directa de las larvas; el único tratamiento efectivo consiste en su extracción endoscópica.

Abstract Anisakiasis is a zoonotic parasitic disease caused by consumption of raw or undercooked fish or seafood infected with nematodes of the Anisakis, Pseudoterranova or Contracaecum genera. Here, we describe the first case of anisakiasis in Colombia and summarize the available literature. A 52-year-old female with a history of abrupt-onset sharp epigastric pain, nausea, vomit, diarrhea, and urticaria following fish consumption consulted the health service. The physical examination revealed moderate tenderness of the epigastric region; the laboratory evaluation showed leukocytosis and a simple X-ray and ECG showed no abnormalities. The diagnosis was made by endoscopic examination, which revealed a thickened gastric wall and a moving larval worm. An Anisakis larva was found and extracted endoscopically, which relieved the pain of the patient. Clinically, anisakiasis may present as a gastric, intestinal, extragastrointestinal or allergic disease. Diagnosis and treatment of anisakiasis are made by a dietary history, direct visualization and endoscopic extraction of possible larvae, which is the only effective therapy.

Dysbiosis Disrupts Gut Immune Homeostasis and Promotes Gastric Diseases.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and also promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in the host, which in turn influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics, chemotherapeutic drugs, and any change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromilieu. Ligands released from dying microbes induce Toll-like receptor (TLR) mimicry, skew hypoxia, and cause sterile inflammation, which further contributes to the severity of inflammatory, autoimmune, and tumorous diseases. The major aim and scope of this review is both to discuss various modalities/interventions across the globe and to utilize microbiota-based therapeutic approaches for mitigating the disease burden.

Upregulation of MUC5AC production and deposition of LEWIS determinants by HELICOBACTER PYLORI facilitate gastric tissue colonization and the maintenance of infection.

BACKGROUND: Helicobacter pylori bacteria colonize human gastric mucosa, cause chronic inflammation, peptic ulcers and gastric cancer. Colonization is mediated by H. pylori adhesins, which preferentially bind mucin 5 (MUC5AC) and Lewis (Le) determinants. The aim of this study was to evaluate the influence of H. pylori and their components on MUC5AC production and deposition of LeX/LeY in gastric epithelial cells in relation to bacterial adhesion using Caviae porcellus primary gastric epithelial cells and an in vivo model of experimental H. pylori infection in these animals. METHODS: MUCA5C and LeX/LeY were induced in vitro by live H. pylori reference strain CCUG 17874 (2 × 107 CFU/ml), H. pylori glycine acid extract (GE), 10 µg/ml; cytotoxin associated gene A (CagA) protein, 1 µl/ml; UreA urease subunit, 5 µg/ml; lipopolysaccharide (LPS) 25 ng/ml and imaged by fluorescence microscopy after anti-MUC5AC or anti-LeX/LeY FITC antibody staining. Bacterial adhesion was imaged by using anti-H. pylori FITC antibodies. The animals were inoculated per os with H. pylori (3 times in 2 days intervals, 1 × 1010 CFU/ml). After 7 or 28 days an infection and inflammation were assessed by histological, serological and molecular methods. Gastric tissue sections of infected and control animals were screend for MUCA5C and LeX, and H. pylori adhesion as above. RESULTS: MUC5AC production and deposition of Lewis determinants, especially LeX were upregulated in the milieu of live H. pylori as well as GE, CagA, UreA or LPS in vitro and in vivo during infection, more effectively in the acute (7 days) than in the chronic (28 days) phase of infection. This was related to enhanced adhesion of H. pylori, which was abrogated by anti-MUC5AC and anti-LeX or anti-LeY antibody treatment. CONCLUSIONS: Modulation of MUCA5C production and LeX/LeY deposition in the gastric mucosa by H. pylori can significantly increase gastric tissue colonization during H. pylori infection.

Crystal-storing Histiocytosis in the Stomach: A Clue to Subtle Hematolymphoid Malignancies.

Crystal-storing histiocytosis (CSH) is an under-recognized entity with a striking association with lymphoproliferative disorders. To study the typical morphologic features of gastric CSH, all lymphomas diagnosed on in-house gastric specimens at The Ohio State University between January 1, 2008 and January 1, 2017 were retrieved. This search yielded 66 specimens from 51 unique patients. All cases were reviewed with CSH identified in 7 stomach biopsies from 4 patients (2 men:2 women; average age, 69 y; range, 56 to 82 y). Endoscopic findings were all abnormal: diffuse nodularity and white discoloration (n=1), patchy nodularity (n=1), and malignant-appearing fundic mass with lymphadenopathy (n=2). We report the typical gastric CSH lesion displays full-thickness expansion of the lamina propria by a lymphohistiocytic infiltrate that distorts the usual gastric glandular architecture. On high power, all cases were defined by the presence of macrophages with abundant eosinophilic cytoplasm containing nonrefractile, nonpolarizable fibrillary cytoplasmic inclusions. Three of the 4 patients had a kappa-restricted lymphoma; the 1 patient with a lambda-restricted lymphoma had the fewest macrophages. Follow-up data were available up to 228 weeks. All 4 patients had persistent/recurrent lymphoma, and 2 patients died of lymphoma-related complications. None of the CSH cases were prospectively recognized as CSH, and 1 case was initially misdiagnosed as a xanthoma. In summary, CSH is an under-recognized lesion historically associated with lymphoproliferative disorders and we found associated with a high mortality in this small series. Since CSH can be so florid as to obscure the concomitant lymphoma, awareness is crucial for accurate diagnosis.

Isolated IgG4-related gastric disease presenting as diffuse gastric wall thickening with ulcer.

An 81-year-old male presented with loss of appetite, early satiety and iron deficiency anaemia. A computed tomography (CT) scan of the abdomen and pelvis during initial work-up revealed diffuse gastric mural thickening associated with a large ulcer and adjacent gastro-hepatic lymphadenopathy. The CT appearances, together with the clinical features, were highly suspicious for an infiltrative type of gastric malignancy. Endoscopic biopsy however showed erosive inflammation, IgG4 plasmacytosis and fibrosis, raising the possibility of IgG4-related disease. A serologic assay for IgG showed normal IgG4 and elevated IgG2 serum levels. After appropriate steroid treatment, endoscopy and CT scan showed resolution of the ulcer and gastric wall thickening. This case shows yet another possible appearance of gastric involvement in IgG4-related disease on the current evolving spectrum of this disease presentation. Greater awareness and education of this disease would help in patient care, ensuring earlier diagnosis, prevention of severe organ damage and morbidity, as well as unnecessary surgery.

Understanding immune phenotypes in human gastric disease tissues by multiplexed immunohistochemistry.

BACKGROUND: Understanding immune phenotypes and human gastric disease in situ requires an approach that leverages multiplexed immunohistochemistry (mIHC) with multispectral imaging to facilitate precise image analyses. METHODS: We developed a novel 4-color mIHC assay based on tyramide signal amplification that allowed us to reliably interrogate immunologic checkpoints, including programmed death-ligand 1 (PD-L1), cytotoxic T cells (CD8+T) and regulatory T cells (Foxp3), in formalin-fixed, paraffin-embedded tissues of various human gastric diseases. By observing cell phenotypes within the disease tissue microenvironment, we were able to determine specific co-localized staining combinations and various measures of cell density. RESULTS: We found that PD-L1 was expressed in gastric ulcer and in tumor cells (TCs), as well as in tumor-infiltrating immune cells (TIICs), but not in normal gastric mucosa or other gastric intraepithelial neoplastic tissues. Furthermore, we found no significant reduction in CD8+T cells, whereas the ratio of CD8+T:Foxp3 cells and CD8+T:PD-L1 cells was suppressed in tumor tissues and elevated in adjacent normal tissues. An unsupervised hierarchical analysis also identified correlations between CD8+T and Foxp3+ tumor-infiltrating lymphocyte (TIL) densities and average PD-L1 levels. Three main groups were identified based on the results of CD8+T:PD-L1 ratios in gastric tumor tissues. Furthermore, integrating CD8+T:Foxp3 ratios, which increased the complexity for immune phenotype status, revealed 6-7 clusters that enabled the separation of gastric cancer patients at the same clinical stage into different risk-group subsets. CONCLUSIONS: Characterizing immune phenotypes in human gastric disease tissues via multiplexed immunohistochemistry may help guide PD-L1 clinical therapy. Observing unique disease tissue microenvironments can improve our understanding of immune phenotypes and cell interactions within these microenvironments, providing the ability to predict safe responses to immunotherapies.

Human and Helicobacter pylori Interactions Determine the Outcome of Gastric Diseases.

The innate immune response is a critical hallmark of Helicobacter pylori infection. Epithelial and myeloid cells produce effectors, including the chemokine CXCL8, reactive oxygen species (ROS), and nitric oxide (NO), in response to bacterial components. Mechanistic and epidemiologic studies have emphasized that dysregulated and persistent release of these products leads to the development of chronic inflammation and to the molecular and cellular events related to carcinogenesis. Moreover, investigations in H. pylori-infected patients about polymorphisms of the genes encoding CXCL8 and inducible NO synthase, and epigenetic control of the ROS-producing enzyme spermine oxidase, have further proven that overproduction of these molecules impacts the severity of gastric diseases. Lastly, the critical effect of the crosstalk between the human host and the infecting bacterium in determining the severity of H. pylori-related diseases has been supported by phylogenetic analysis of the human population and their H. pylori isolates in geographic areas with varying clinical and pathologic outcomes of the infection.

A rare case of IgG4-related disease: a gastric mass, associated with regional lymphadenopathy.

BACKGROUND: IgG4-related disease (IgG4-RD) is a newly recognized disorder, characterized by massive IgG4+ lymphocyte and plasma cell infiltration, storiform fibrosis, causing enlargement, nodules or thickening of the various organs, simultaneously or metachronously. Involvement of the gastrointestinal tract is very rare and can be presented as a diffuse wall thickening or polyp or mass-like lesion. Up to now, there have been reported only a few cases of isolated gastric IgG4-RD. CASE PRESENTATION: We present an unusual case of IgG4-RD of the stomach with involvement of the regional lymph nodes, clinically manifested as a gastric cancer with related pyloric stenosis. The patient underwent distal gastrectomy, omentectomy and lymph node dissection. The postoperative serum IgG4 level was increased. The diagnosis was confirmed by immunohistochemical study. CONCLUSIONS: In the most of the reported cases there was not sufficient data about the regional lymph nodal status, although the majority of the patients had been operated with presumptive diagnosis of gastric neoplasm. Our case is rare and valuable because it presents a gastric IgG4-related lesion larger than all previously reported in literature, and IgG4-related lymphadenopathy, confirmed histologically, which contributes to better knowledge of the disease.

Acute Graft-versus-Host Disease: Novel Biological Insights.

Graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent insights into intestinal homeostasis and uncovering of new pathways and targets have greatly reconciled our understanding of GVHD pathophysiology and will reshape contemporary GVHD prophylaxis and treatment. Gastrointestinal (GI) GVHD is the major cause of mortality. Emerging data indicate that intestinal stem cells (ISCs) and their niche Paneth cells are targeted, resulting in dysregulation of the intestinal homeostasis and microbial ecology. The microbiota and their metabolites shape the immune system and intestinal homeostasis, and they may alter host susceptibility to GVHD. Protection of the ISC niche system and modification of the intestinal microbiota and metabolome to restore intestinal homeostasis may, thus, represent a novel approach to modulate GVHD and infection. Damage to the intestine plays a central role in amplifying systemic GVHD by propagating a proinflammatory cytokine milieu. Molecular targeting to inhibit kinase signaling may be a promising approach to treat GVHD, ideally via targeting the redundant effect of multiple cytokines on immune cells and enterocytes. In this review, we discuss insights on the biology of GI GVHD, interaction of microflora and metabolome with the hosts, identification of potential new target organs, and identification and targeting of novel T cell-signaling pathways. Better understanding of GVHD biology will, thus, pave a way to develop novel treatment strategies with great clinical benefits.

IMMUNOMODULATORY EFFECT OF ALLOGENEIC MESENCHYMAL STEM CELLS OF RATS.

INTRODUCTION: Recently, more and more attracted the attention of cell therapy, which requires a study of the efficacy and safety of allogeneic MSCs transplantation in acute and chronic inflammatory reactions. The aim of our study was to examine the effectiveness of transplantation of allogeneic mesenchymal bone marrow stromal cells for the healing of surgical wounds the glandular stomach in rats. MATERIAL AND METHODS: Using white Wistar rats. Producing cell transplantation mononuclear fraction derived from rat bone marrow aspirate. Injected cells 8 and 9 th passage. The dose of cells administered to 3-th and / or 7-th days 3,5h106 cells / ml twice or 5,0h106 cells / ml dose. Autopsy on day 10-th and 17-th. The serum ELISA determined the content of the pro- and anti-inflammatory cytokines IL1ß, TNFα, IFNy, IL-4. RESULTS AND DISCUSSION: Introduction MSCs contributed to the decline of the immune mediators of inflammation IL1P, TNFa, IFNy, increase anti-inflammatory IL4. Quality improved healing. CONCLUSION: Rapid curative effect of stem cells may be associated with the formation of blood immune cells (macrophages) that produce substances that restore damaged tissue. They restore the balance between Th1 and Th2.

Gastric presentation (vasculitis) mimics a gastric cancer as initial symptom in granulomatosis with polyangiitis: a case report and review of the literature.

Granulomatosis with polyangiitis (GPA), formerly called Wegener's Granulomatosis, is characterized by necrotizing granulomatous inflammation and belongs to the family of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. The main clinical symptoms of GPA are vasculitis primarily involving upper and lower respiratory tracts, as well as kidneys. Gastrointestinal manifestations of GPA are less common (0-20 %), with gastric presentation mimicking a gastric cancer as an initial symptom. This is a descriptive case report of one patient, together with systematic review of the literature. We described a 31-year-old Chinese woman who presented with complaints of abdominal distention, anorexia for 2 months. Gastroscopy was carried out for three times, and stomach cancer was suspected. However, histopathology of gastric biopsy revealed a chronic inflammation with mucosal ulceration, frequent neutrophils and lymphocytes infiltration, and local granulomatous formation, whereas no sign of stomach carcinoma was observed. In view of the positive cANCA test, a diagnosis of GPA was considered. From the onset of the GPA in the patients, no other organs have been involved in the disease. The patient was successfully treated with corticosteroids and cyclophosphamide. As shown in the report, patients who present only with gastrointestinal manifestations represent challenges to diagnosis. ANCA testing can serve as a decisive diagnostic tool. Although uncommon, GI involvement may be a major feature in GPA, sometimes presenting as gastric tumor-like lesions. Diagnosis should be considered in patients presenting with GI symptoms accompanied by evidence of systemic vasculitis, and ANCA test should be used as a diagnostic measurement to clarify differential diagnosis.

Are gastric mucosal macrophages responsible for gastric injury in acute pancreatitis?

AIM: To investigate the protective effect of clodronate-containing liposomes against severe acute pancreatitis (SAP)-triggered acute gastric mucosal injury (AGMI) in rats. METHODS: Clodronate- and phosphate-buffered saline (PBS)-containing liposomes were prepared by reverse-phase evaporation. The SAP rat model was established by injecting sodium taurocholate into the pancreatic subcapsular space. Sprague-Dawley rats were randomly divided into three groups: control (C), SAP plus PBS-containing liposome (P) and SAP plus clodronate-containing liposome (T). Serum tumor necrosis factor (TNF)-α levels were estimated by ELISA. Pathological changes in the gastric mucosa and pancreas were observed by hematoxylin and eosin (HE) staining. Apoptotic cells were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The numbers of macrophages in the gastric mucosa were analyzed by CD68 immunohistochemical staining. RESULTS: The liposomes had a mean diameter of 150 ± 30 nm. The TNF-α levels were significantly higher in the P group than that in the C group (2 h, 145.13 ± 11.50 vs 23.2 ± 2.03; 6 h, 245.06 ± 12.11 vs 30.28 ± 6.07, P < 0.05), and they were significantly lower in the T group than that in the P group (2 h, 93.24 ± 23.11 vs 145.13 ± 11.50; 6 h, 135.18 ± 13.10 vs 245.06 ± 12.11, P < 0.05). The pathological scores of the pancreas were lower in the T group than in the P group (2 h, 1.88 ± 0.83 vs 4.13 ± 0.83; 6 h, 2.87 ± 0.64 vs 6.25 ± 0.88, P < 0.01). The pathological scores of the gastric mucosa were also lower in the T group than in the P group (2 h, 1.12 ± 0.64 vs 2 ± 0.75; 6 h, 1.58 ± 0.53 vs 3 ± 1.31, P < 0.05). In addition, increased CD68 levels were observed in the gastric mucosa of the P group compared with the C group. Clodronate-containing liposomes decreased the CD68 levels in the mucosa of the T group. The apoptotic indexes of the gastric mucosa were higher in the T group than in the P group (2 h, 15.7 ± 0.92 vs 11.5 ± 1.64; 6 h, 21.12 ± 1.06 vs 12.6 ± 2.44, P < 0.01). CONCLUSION: Gastric macrophages contribute to the pathogenesis of gastric injury in SAP. Clodronate-containing liposomes have protective effects against AGMI in rats with SAP.

The effect of thalidomide on ethanol-induced gastric mucosal damage in mice: involvement of inflammatory cytokines and nitric oxide.

Excessive ethanol ingestion causes gastric mucosal damage through the inflammatory and oxidative processes. The present study was aimed to evaluate the protective effect of thalidomide on ethanol-induced gastric mucosal damage in mice. The animals were pretreated with vehicle or thalidomide (30 or 60 mg/kg, orally), and one hour later, the gastric mucosal injury was induced by oral administration of acidified ethanol. The animals were euthanized one hour after ethanol ingestion, and gastric tissues were collected to biochemical analyzes. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed that treatment of mice with thalidomide prior to the administration of ethanol dose-dependently reduced the gastric ulcer index. Thalidomide pretreatment significantly reduced the levels of pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6], malondialdehyde (MDA) and myeloperoxidase (MPO) activity. In addition, thalidomide significantly inhibited ethanol-induced nitric oxide (NO) overproduction in gastric tissue. Histological observations showed that ethanol-induced gastric mucosal damage was attenuated by thalidomide pretreatment. It seems that thalidomide as an anti-inflammatory agent may have a protective effect against alcohol-induced mucosal damage by inhibition of neutrophil infiltration and reducing the production of nitric oxide and inflammatory cytokines in gastric tissue.

Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence.

Parasitic helminths reside in immunologically-exposed extracellular locations within their hosts, yet they are capable of surviving for extended periods. To enable this survival, these parasites have developed complex and multifaceted mechanisms to subvert or suppress host immunity. This review summarises current knowledge of immune modulation by helminth parasites of ruminants and the parasite-derived molecules involved in driving this modulation. Such immunomodulatory molecules have considerable promise as vaccine targets, as neutralisation of their function is predicted to enhance anti-parasite immunity and, as such, current knowledge in this area is presented herein. Furthermore, we summarise current evidence that, as well as affecting parasite-specific immunity, immune modulation by these parasites may also affect the ability of ruminant hosts to control concurrent diseases or mount effective responses to vaccination.

Post-infectious irritable bowel syndrome: mechanistic insights into chronic disturbances following enteric infection.

Irritable bowel syndrome (IBS) is a commonly encountered chronic functional gastrointestinal (GI) disorder. Approximately 10% of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery. The appearance of new IBS symptoms following an infectious event is defined as post-infectious-IBS. Indeed, with the World Health Organization estimating between 2 and 4 billion cases annually, infectious diarrheal disease represents an incredible international healthcare burden. Additionally, compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features. A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota, epithelial barrier integrity, effector cell functions, and innate and adaptive immune features, all proposed physiological manifestations that can underlie GI abnormalities in IBS. Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms, and illicit successful infections. Consequently, the impact of infectious events on host physiology can be multidimensional in terms of anatomical location, functional scope, and duration. This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease, but may also lead to the establishment of chronic GI dysfunction compatible with IBS.